What is the Mutation in FMR1 That Causes Fragile X Syndrome?

FMR1 (fragile X mental retardation 1) is the gene that contains the genetic information for how to synthesize FMRP (fragile X mental retardation protein). Fragile X syndrome occurs when FMRP is missing. 

The FMR1 gene is located in the DNA on the X chromosome. The specific location is given as Xq27.3. That means it is on the X chromosome (X), it is on the long arm (q) and it is at the far end (27.3).

Genetic information in humans is stored in an odd way. Buried within the information that is actually used is lots of information that is not used. 

Imagine that you went to the library and found that in the chapter you were interested in, many of the pages contained random letters. You photocopied the entire chapter, including the pages that contained no useful information. Before you left the library, you tossed all the pages with random letters in a recycling bin and only took home the pages with words you could read.

In a similar way, our genes are interspersed with spacers called introns. These introns may play an important role but do not contain information that will be used to make a protein. 

To make a protein, we first make a copy of the DNA (mRNA). That mRNA will used as a pattern for assembling a protein. When we copy the DNA into mRNA, we initially copy both these introns and the information we are going to actually use (exons). The introns must be edited out before the mRNA's can actually be used to coordinate the synthesis of proteins.

The FMR1 gene itself takes up 38,000 base pairs of DNA. But as shown in the drawing below, most of the gene is made up of introns (indicated by the yellow color). Only a small part of the information in the gene (the black exons) will be used to make the FMRP. The edited mRNA has only 4000 of the original 38,000 bases.

The location of the mutation that sets in motion fragile X syndrome is near the beginning of the FMR1 gene. In this location, there is normally a series of about 30 repeats of CGG. In individuals with the premutation, there are from 55-200 of these repeats. Persons with the full mutation have more than 200 of the CGG repeats.

Reproduced with permission. Stephen T. Warren. Trinucleotide Repetition and fragile X Syndrome. Hospital Practice 1997; 32(4):73. Copyright The McGraw-Hill Companies, Inc. Illustration by Seward Hung.

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This page last updated Saturday, November 04, 2006